Filamentary devices having a flexible joint for treatment of vascular defects

ABSTRACT

Devices and methods for treatment of a patient&#39;s vasculature are described. Embodiments may include a permeable implant having a radially constrained state configured for delivery within a catheter lumen, an expanded state, and a plurality of elongate filaments that are woven together. The implant may include first and second permeable shells. The first permeable shell having a proximal end with a concave or recessed section and a second permeable shell having a convex section that mates with the concave or recessed section. The implant also includes a flexible, articulating joint between the first and second permeable shells.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. § 119(e)from U.S. Provisional Application Ser. No. 62/819,317, filed Mar. 15,2019, which is hereby incorporated by reference in its entirety for allpurposes.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

FIELD OF THE INVENTION

Embodiments of devices and methods herein are directed to blocking aflow of fluid through a tubular vessel or into a small interior chamberof a saccular cavity or vascular defect within a mammalian body. Morespecifically, embodiments herein are directed to devices and methods fortreatment of a vascular defect of a patient including some embodimentsdirected specifically to the treatment of cerebral aneurysms ofpatients.

BACKGROUND

The mammalian circulatory system is comprised of a heart, which acts asa pump, and a system of blood vessels which transport the blood tovarious points in the body. Due to the force exerted by the flowingblood on the blood vessel the blood vessels may develop a variety ofvascular defects. One common vascular defect known as an aneurysmresults from the abnormal widening of the blood vessel. Typically,vascular aneurysms are formed as a result of the weakening of the wallof a blood vessel and subsequent ballooning and expansion of the vesselwall. If, for example, an aneurysm is present within an artery of thebrain, and the aneurysm should burst with resulting cranialhemorrhaging, death could occur.

Surgical techniques for the treatment of cerebral aneurysms typicallyinvolve a craniotomy requiring creation of an opening in the skull ofthe patient through which the surgeon can insert instruments to operatedirectly on the patient's brain. For some surgical approaches, the brainmust be retracted to expose the parent blood vessel from which theaneurysm arises. Once access to the aneurysm is gained, the surgeonplaces a clip across the neck of the aneurysm thereby preventingarterial blood from entering the aneurysm. Upon correct placement of theclip the aneurysm will be obliterated in a matter of minutes. Surgicaltechniques may be effective treatment for many aneurysms. Unfortunately,surgical techniques for treating these types of conditions include majorinvasive surgical procedures which often require extended periods oftime under anesthesia involving high risk to the patient. Suchprocedures thus require that the patient be in generally good physicalcondition in order to be a candidate for such procedures.

Various alternative and less invasive procedures have been used to treatcerebral aneurysms without resorting to major surgery. One approach totreating aneurysms without the need for invasive surgery involves theplacement of sleeves or stents into the vessel and across the regionwhere the aneurysm occurs. Such devices maintain blood flow through thevessel while reducing blood pressure applied to the interior of theaneurysm. Certain types of stents are expanded to the proper size byinflating a balloon catheter, referred to as balloon expandable stents,while other stents are designed to elastically expand in aself-expanding manner. Some stents are covered typically with a sleeveof polymeric material called a graft to form a stent-graft. Stents andstent-grafts are generally delivered to a preselected position adjacenta vascular defect through a delivery catheter. In the treatment ofcerebral aneurysms, covered stents or stent-grafts have seen verylimited use due to the likelihood of inadvertent occlusion of smallperforator vessels that may be near the vascular defect being treated.

In addition, current uncovered stents are generally not sufficient as astand-alone treatment. In order for stents to fit through themicrocatheters used in small cerebral blood vessels, their density isusually reduced such that when expanded there is only a small amount ofstent structure bridging the aneurysm neck. Thus, they do not blockenough flow to cause clotting of the blood in the aneurysm and are thusgenerally used in combination with vaso-occlusive devices, such as thecoils discussed above, to achieve aneurysm occlusion.

Some procedures involve the delivery of embolic or filling materialsinto an aneurysm. The delivery of such vaso-occlusion devices ormaterials may be used to promote hemostasis or fill an aneurysm cavityentirely. Vaso-occlusion devices may be placed within the vasculature ofthe human body, typically via a catheter, either to block the flow ofblood through a vessel with an aneurysm through the formation of anembolus or to form such an embolus within an aneurysm stemming from thevessel. A variety of implantable, coil-type vaso-occlusion devices areknown. The coils of such devices may themselves be formed into asecondary coil shape, or any of a variety of more complex secondaryshapes. Vaso-occlusive coils are commonly used to treat cerebralaneurysms but suffer from several limitations including poor packingdensity, compaction due to hydrodynamic pressure from blood flow, poorstability in wide-necked aneurysms, and complexity and difficulty in thedeployment thereof as most aneurysm treatments with this approachrequire the deployment of multiple coils. Coiling is less effective attreating certain physiological conditions, such as wide neck cavities(e.g. wide neck aneurysms) because there is a greater risk of the coilsmigrating out of the treatment site.

A number of aneurysm neck bridging devices with defect spanning portionsor regions have been attempted, however, none of these devices have hada significant measure of clinical success or usage. A major limitationin their adoption and clinical usefulness is the inability to positionthe defect spanning portion to assure coverage of the neck. Existingstent delivery systems that are neurovascular compatible (i.e.deliverable through a microcatheter and highly flexible) do not have thenecessary rotational positioning capability. Another limitation of manyaneurysm bridging devices described in the prior art is the poorflexibility. Cerebral blood vessels are tortuous, and a high degree offlexibility is required for effective delivery to most aneurysmlocations in the brain.

What has been needed are devices and methods for delivery and use insmall and tortuous blood vessels that can substantially block the flowof blood into an aneurysm, such as a cerebral aneurysm, with a decreasedrisk of inadvertent aneurysm rupture or blood vessel wall damage. Inaddition, what has been needed are methods and devices suitable forblocking blood flow in cerebral aneurysms over an extended period oftime without a significant risk of deformation, compaction ordislocation.

Intrasaccular occlusive devices are part of a newer type of occlusiondevice used to treat various intravascular conditions includinganeurysms. They are often more effective at treating these wide neckconditions, or larger treatment areas. The intrasaccular devicescomprise a structure which sits within the aneurysm and provides anocclusive effect at the neck of the aneurysm to help limit blood flowinto the aneurysm. The rest of the device comprises a relativelyconformable structure that sits within the aneurysm helping to occludeall or a portion of the aneurysm. Intrasaccular devices typicallyconform to the shape of the treatment site. These devices also occludethe cross section of the neck of the treatment site/aneurysm, therebypromoting clotting and causing thrombosis and closing of the aneurysmover time. In larger aneurysms, there is a risk of compaction where theintrasaccular device can migrate into the aneurysm and leave the neckregion.

Many intrasaccular devices are best suited to treat bifurcationaneurysms (aneurysms located along a vessel bifurcation) rather thansidewall aneurysms (which are located along a sidewall of a vessel), fora few reasons. First, while access into a bifurcation aneurysm isrelatively straightforward given that catheter access occurs directlyalong the parent artery that leads into the bifurcation aneurysm, thisis more complicated in a sidewall aneurysm where the catheter has to beangled into the aneurysm. In practice, this means that it is likely thatthe intrasaccular device may be delivered at an offset angle into thesidewall aneurysm in a number of circumstances. Second, the proximal endof some intrasaccular devices may be stiff due to the presence of, e.g.,the braided wires comprising the implant being bundled together at aproximal terminus. The stiffness of the connection of the intrasacculardevice with the pusher of the delivery system can hamper delivery of theintrasaccular device into sidewall aneurysms. Delivery into sidewallaneurysms (e.g., at about a 90° angle to the parent artery—though thiscan vary depending on the geometry of the sidewall aneurysm) requires aflexible connection between the pusher and implant while maintaining thepushability, trackability, and retrievable properties of theintrasaccular device.

Though intrasaccular devices offer some advantages in occluding targetareas such as aneurysms, due to the tight geometry associated with thevasculature, it can be difficult to ensure that part of theintrasaccular devices does not stick out into the parent artery. It canalso be difficult to sufficiently occlude flow at the neck of theaneurysm/treatment site. Furthermore, it can be difficult to configurean intrasaccular device that can effectively treat sidewall aneurysms.There is a need for an intrasaccular device that mitigates or preventsthese issues.

SUMMARY

Intrasaccular device delivery into a sidewall aneurysm can be difficultfor several reasons, as outlined above. For instance, the deliverycatheter has to often be delivered at an odd angle due to the geometryof the sidewall aneurysm, making it difficult to correctly deliver anddeploy the intrasaccular device. Furthermore, the proximal end of someintrasaccular devices may be stiff due to the presence of, e.g., implantwires being bundled together. The stiffness of the connection of theintrasaccular device with the pusher of the delivery system can hamperdelivery of the intrasaccular device into sidewall aneurysms. Deliveryinto sidewall aneurysms (e.g., at a 90° angle to the parent artery)requires a flexible connection between the pusher and implant whilemaintaining the pushability, trackability, and retrievable properties ofthe intrasaccular device. Devices are described herein that addressthese problems by including a flexible connection between the pusher andthe implant.

Devices are also described that increase proximal stability of thedevice and promotes proper seating of the device in the treatmentlocation.

Devices are also described that further improve metal surface coverageat the proximal end of the device, thereby preventing compaction of thedevice.

An intrasaccular occlusive device is described. In one embodiment, theintrasaccular occlusive device has a first occlusive section thatoccludes the target structure, and a second occlusive section attachedto the first occlusive section. The second occlusive section is meant tosit at the neck of the target region, thereby occluding flow at the necksection while also conforming to the neck shape such that it setsat/within this neck shape. In one embodiment, the first and secondocclusive sections comprise a mesh of braided wires. In one embodiment,the first occlusive section includes a proximal dimpled region, and thesecond occlusive section is configured to fit within this proximaldimpled region. In one embodiment, the first occlusive section includesa proximal dimpled region with a stem, and the second occlusive sectionconnects to the stem of the proximal dimpled region.

The intrasaccular devices could be used to treat bifurcation aneurysmslocated at ICA terminus, AComm, and MCA bifurcations. Devices are alsodescribed that aid in the delivery of intrasaccular devices intosidewall aneurysms.

In one embodiment, a device for treatment of a patient's cerebralaneurysm is described. The device includes a first permeable shellhaving a proximal end, a distal end, a radially constrained elongatedstate configured for delivery within a catheter lumen, an expanded statewith a longitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, the expanded state having a proximal end with arecessed section; and a second permeable shell having a proximal end, adistal end, a radially constrained elongated state configured fordelivery within a catheter lumen, an expanded state with alongitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, wherein the expanded state of the secondpermeable shell is configured to sit within the recessed section of thefirst permeable shell. The proximal end of the first permeable shell iscoupled with the distal end of the second permeable shell.

In another embodiment, a cerebral sidewall aneurysm treatment device isdescribed. The device includes a first permeable shell having a proximalend, a distal end, a radially constrained elongated state configured fordelivery within a catheter lumen, an expanded state with alongitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, the expanded state having a proximal end with arecessed section; and a second permeable shell having a proximal end, adistal end, a radially constrained elongated state configured fordelivery within a catheter lumen, an expanded state with alongitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, wherein the distal end of the second permeableshell is coupled to the proximal end of the first permeable shell, andwherein the proximal end of the second permeable shell is coupled with adelivery pusher. The second permeable shell is configured to exert forceagainst the recessed section of the first permeable shell in order toposition the first permeable shell over a neck region of the cerebralsidewall aneurysm.

In another embodiment, a device for treatment of a patient's cerebralaneurysm is described. The device includes a first permeable shellhaving a proximal end, a distal end, a radially constrained elongatedstate configured for delivery within a catheter lumen, an expanded statewith a longitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, the expanded state having a proximal end with arecessed section adapted to sit over a neck of an aneurysm; and a secondpermeable shell having a proximal end, a distal end, a radiallyconstrained elongated state configured for delivery within a catheterlumen, an expanded state with a longitudinally shortened configurationrelative to the radially constrained state, and a plurality of elongatefilaments that are woven together to form a mesh, wherein the distal endof the second permeable shell is coupled with the proximal end of thefirst permeable shell. The second permeable shell is configured tooccupy the recessed section of the first permeable shell to augmentsurface coverage over the neck of the aneurysm.

In another embodiment, a method for treating a cerebral aneurysm havingan interior cavity and a neck is described. The method includes the stepof advancing an implant in a microcatheter to a region of interest in acerebral artery. The implant comprises a first permeable shell having aproximal end, a distal end, a radially constrained elongated stateconfigured for delivery within a lumen of the microcatheter, an expandedstate with a longitudinally shortened configuration relative to theradially constrained state, and a plurality of elongate filaments thatare woven together to form a mesh, the expanded state having a proximalend with a concave section; and a second permeable shell having aproximal end, a distal end, a radially constrained elongated stateconfigured for delivery within the lumen of the microcatheter, anexpanded state with a longitudinally shortened configuration relative tothe radially constrained state, and a plurality of elongate filamentsthat are woven together to form a mesh, wherein the expanded state ofthe second permeable shell is configured to sit within the concavesection of the first permeable shell, wherein the distal end of thesecond permeable shell is coupled with the proximal end of the firstpermeable shell. The first permeable shell is then deployed within thecerebral aneurysm, wherein the first permeable shell expands to theexpanded state in the interior cavity of the aneurysm. The secondpermeable shell is then deployed, wherein the second permeable shellexpands to the expanded state and sits within the concave section of thefirst permeable shell. The microcatheter is then withdrawn from theregion of interest after deploying the second permeable shell.

In another embodiment, a device for treatment of a patient's cerebralaneurysm is described. The device includes a first permeable shellhaving a proximal end, a distal end, a radially constrained elongatedstate configured for delivery within a catheter lumen, an expanded statewith a longitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, the expanded state having a proximal end with aconcave section; and a second permeable shell having a proximal end, adistal end, a radially constrained elongated state configured fordelivery within a catheter lumen, an expanded state with alongitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, wherein the expanded state of the secondpermeable shell is configured to sit within the concave section of thefirst permeable shell. The proximal end of the first permeable shell iscoupled with the distal end of the second permeable shell.

In another embodiment, methods for treating a cerebral aneurysm havingan interior cavity and a neck are described. The methods include thestep of advancing an implant in a microcatheter to a region of interestin a cerebral artery, wherein the implant comprises a first permeableshell having a proximal end, a distal end, a radially constrainedelongated state configured for delivery within a lumen of themicrocatheter, an expanded state with a longitudinally shortenedconfiguration relative to the radially constrained state, and aplurality of elongate filaments that are woven together to form a mesh,the expanded state having a proximal end with a concave section; and asecond permeable shell having a proximal end, a distal end, a radiallyconstrained elongated state configured for delivery within the lumen ofthe microcatheter, an expanded state with a longitudinally shortenedconfiguration relative to the radially constrained state, and aplurality of elongate filaments that are woven together to form a mesh,wherein the expanded state of the second permeable shell is configuredto sit within the concave section of the first permeable shell. Theproximal end of the first permeable shell is coupled with the distal endof the second permeable shell. The first permeable shell is thendeployed within the cerebral aneurysm, wherein the first permeable shellexpands to the expanded state in the interior cavity of the aneurysm.The second permeable shell is then deployed, wherein the secondpermeable shell expands to the expanded state and sits within theconcave section of the first permeable shell. The microcatheter is thenwithdrawn from the region of interest after deploying the secondpermeable shell.

In one embodiment, a device for treatment of a patient's cerebralaneurysm is described. The device includes a first permeable shell and asecond permeable shell. The first permeable shell has a proximal end, adistal end, a radially constrained elongated state configured fordelivery within a catheter lumen, an expanded state with alongitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh. The expanded state has a proximal end with aconcave section. The second permeable shell has a proximal end, a distalend, a radially constrained elongated state configured for deliverywithin a catheter lumen, a first expanded state, a second expandedstate, and a plurality of elongate filaments that are woven together toform a mesh, wherein the second expanded state of the second permeableshell is configured to sit within the concave section of the firstpermeable shell. The proximal end of the first permeable shell iscoupled with the distal end of the second permeable shell.

In another embodiment, methods for treating a cerebral aneurysm havingan interior cavity and a neck are described. The methods include thestep of advancing an implant in a microcatheter to a region of interestin a cerebral artery, wherein the implant comprises a first permeableshell and a second permeable shell. The first permeable shell has aproximal end, a distal end, a radially constrained elongated stateconfigured for delivery within a catheter lumen, an expanded state witha longitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh. The expanded state has a proximal end with aconcave section. The second permeable shell has a proximal end, a distalend, a radially constrained elongated state configured for deliverywithin a catheter lumen, a first expanded state, a second expandedstate, and a plurality of elongate filaments that are woven together toform a mesh, wherein the second expanded state of the second permeableshell is configured to sit within the concave section of the firstpermeable shell. The proximal end of the first permeable shell iscoupled with the distal end of the second permeable shell. The firstpermeable shell is then deployed within the cerebral aneurysm, whereinthe first permeable shell expands to the expanded state in the interiorcavity of the aneurysm. The second permeable shell is then deployed,wherein the second permeable shell expands to the first expanded state.The microcatheter is then withdrawn from the region of interest afterthe second permeable shell assumes the second expanded state and sitswithin the concave section of the first permeable shell.

In some embodiments, the first and second permeable shells may becoupled together, wherein juncture of the coupling serves as a flexiblejoint around which the first permeable shell can pivot and deflectrelative to the second permeable shell. The first and second permeableshells may be coupled together with an elongate braided mesh. Theflexible joint between the first and second permeable shell allows forthe first permeable shell to deflect at an angle of up to about 180°,alternatively up to about 150°, alternatively up to about 120°,alternatively up to about 90°, alternatively up to about 60°,alternatively up to about 45°, alternatively up to about 30°,alternatively up to about 10° relative to a longitudinal axis of thesecond permeable shell. In some embodiments, the deflection orarticulation highlighted above can help position or stabilize anintrasaccular device for delivery into a sidewall aneurysm.

In some embodiments, the second permeable shell may have an expandedconvex shape that is configured to mate with the proximal concave orrecessed section of the expanded state of the first permeable shell. Insome embodiments, the second permeable shell is fully contained withinthe proximal concave cavity of the first permeable shell, i.e., thesecond permeable shell does not extend proximally past a plane definedby the proximal most edge of the first permeable shell when both thefirst and second permeable shells are in their expanded states. In otherembodiments, the second permeable shell may be even with the planedefined by the proximal most edge of the first permeable shell when boththe first and second permeable shells are in their expanded states. Inother embodiments, the second permeable shell may extend proximallybeyond the plane defined by the proximal most edge of the firstpermeable shell when both the first and second permeable shells are intheir expanded states.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an elevation view of an embodiment of a device for treatmentof a patient's vasculature and a plurality of arrows indicating inwardradial force.

FIG. 2 is an elevation view of a beam supported by two simple supportsand a plurality of arrows indicating force against the beam.

FIG. 3 is a bottom perspective view of an embodiment of a device fortreatment of a patient's vasculature.

FIG. 4 is an elevation view of the device for treatment of a patient'svasculature of FIG. 3.

FIG. 5 is a transverse cross sectional view of the device of FIG. 4taken along lines 5-5 in FIG. 4.

FIG. 6 shows the device of FIG. 4 in longitudinal section taken alonglines 6-6 in FIG. 4.

FIG. 7 is an enlarged view of the woven filament structure taken fromthe encircled portion 7 shown in FIG. 5.

FIG. 8 is an enlarged view of the woven filament structure taken fromthe encircled portion 8 shown in FIG. 6.

FIG. 9 is a proximal end view of the device of FIG. 3.

FIG. 10 is a transverse sectional view of a proximal hub portion of thedevice in FIG. 6 indicated by lines 10-10 in FIG. 6.

FIG. 11 is an elevation view in partial section of a distal end of adelivery catheter with the device for treatment of a patient'svasculature of FIG. 3 disposed therein in a collapsed constrained state.

FIG. 12 illustrates an embodiment of a filament configuration for adevice for treatment of a patient's vasculature.

FIG. 13 illustrates a device for treatment of a patient's vasculature.

FIG. 14 illustrates a device for treatment of a patient's vasculaturethat includes multiple permeable shells.

FIG. 15 illustrates the device for treatment of a patient's vasculaturefrom FIG. 14 with the second permeable shell in a first expanded state.

FIGS. 16A-16E illustrates the device of FIG. 15 being delivered into asidewall aneurysm.

FIG. 17 is a schematic view of a patient being accessed by an introducersheath, a microcatheter and a device for treatment of a patient'svasculature releasably secured to a distal end of a delivery device oractuator.

FIG. 18 is a sectional view of a terminal aneurysm.

FIG. 19 is a sectional view of an aneurysm.

FIG. 20 is a schematic view in section of an aneurysm showingperpendicular arrows which indicate interior nominal longitudinal andtransverse dimensions of the aneurysm.

FIG. 21 is a schematic view in section of the aneurysm of FIG. 20 with adashed outline of a device for treatment of a patient's vasculature in arelaxed unconstrained state that extends transversely outside of thewalls of the aneurysm.

FIG. 22 is a schematic view in section of an outline of a devicerepresented by the dashed line in FIG. 21 in a deployed and partiallyconstrained state within the aneurysm.

FIGS. 23-26 show a deployment sequence of a device for treatment of apatient's vasculature.

FIG. 27 is an elevation view in partial section of an embodiment of adevice for treatment of a patient's vasculature deployed within ananeurysm at a tilted angle.

FIG. 28 is an elevation view in partial section of an embodiment of adevice for treatment of a patient's vasculature deployed within anirregularly shaped aneurysm.

FIG. 29 shows an elevation view in section of a device for treatment ofa patient's vasculature deployed within a vascular defect aneurysm.

DETAILED DESCRIPTION

Discussed herein are devices and methods for the treatment of vasculardefects that are suitable for minimally invasive deployment within apatient's vasculature, and particularly, within the cerebral vasculatureof a patient. For such embodiments to be safely and effectivelydelivered to a desired treatment site and effectively deployed, somedevice embodiments may be configured for collapse to a low profileconstrained state with a transverse dimension suitable for deliverythrough an inner lumen of a microcatheter and deployment from a distalend thereof. Embodiments of these devices may also maintain a clinicallyeffective configuration with sufficient mechanical integrity oncedeployed so as to withstand dynamic forces within a patient'svasculature over time that may otherwise result in compaction of adeployed device. It may also be desirable for some device embodiments toacutely occlude a vascular defect of a patient during the course of aprocedure in order to provide more immediate feedback regarding successof the treatment to a treating physician.

Intrasaccular occlusive devices that include a permeable shell formedfrom a woven or braided mesh have been described in US 2017/0095254, US2016/0249934, US 2016/0367260, US 2016/0249937, and US 2018/0000489, allof which are hereby expressly incorporated by reference in theirentirety for all purposes.

Some embodiments are particularly useful for the treatment of cerebralaneurysms by reconstructing a vascular wall so as to wholly or partiallyisolate a vascular defect from a patient's blood flow. Some embodimentsmay be configured to be deployed within a vascular defect to facilitatereconstruction, bridging of a vessel wall or both in order to treat thevascular defect. For some of these embodiments, the permeable shell ofthe device may be configured to anchor or fix the permeable shell in aclinically beneficial position. For some embodiments, the device may bedisposed in whole or in part within the vascular defect in order toanchor or fix the device with respect to the vascular structure ordefect. The permeable shell may be configured to span an opening, neckor other portion of a vascular defect in order to isolate the vasculardefect, or a portion thereof, from the patient's nominal vascular systemin order allow the defect to heal or to otherwise minimize the risk ofthe defect to the patient's health.

For some or all of the embodiments of devices for treatment of apatient's vasculature discussed herein, the permeable shell may beconfigured to allow some initial perfusion of blood through thepermeable shell. The porosity of the permeable shell may be configuredto sufficiently isolate the vascular defect so as to promote healing andisolation of the defect, but allow sufficient initial flow through thepermeable shell so as to reduce or otherwise minimize the mechanicalforce exerted on the membrane the dynamic flow of blood or other fluidswithin the vasculature against the device. For some embodiments ofdevices for treatment of a patient's vasculature, only a portion of thepermeable shell that spans the opening or neck of the vascular defect,sometimes referred to as a defect spanning portion, need be permeableand/or conducive to thrombus formation in a patient's bloodstream. Forsuch embodiments, that portion of the device that does not span anopening or neck of the vascular defect may be substantiallynon-permeable or completely permeable with a pore or openingconfiguration that is too large to effectively promote thrombusformation.

In general, it may be desirable in some cases to use a hollow, thinwalled device with a permeable shell of resilient material that may beconstrained to a low profile for delivery within a patient. Such adevice may also be configured to expand radially outward upon removal ofthe constraint such that the shell of the device assumes a larger volumeand fills or otherwise occludes a vascular defect within which it isdeployed. The outward radial expansion of the shell may serve to engagesome or all of an inner surface of the vascular defect wherebymechanical friction between an outer surface of the permeable shell ofthe device and the inside surface of the vascular defect effectivelyanchors the device within the vascular defect. Some embodiments of sucha device may also be partially or wholly mechanically captured within acavity of a vascular defect, particularly where the defect has a narrowneck portion with a larger interior volume. In order to achieve a lowprofile and volume for delivery and be capable of a high ratio ofexpansion by volume, some device embodiments include a matrix of wovenor braided filaments that are coupled together by the interwovenstructure so as to form a self-expanding permeable shell having a poreor opening pattern between couplings or intersections of the filamentsthat is substantially regularly spaced and stable, while still allowingfor conformity and volumetric constraint.

As used herein, the terms woven and braided are used interchangeably tomean any form of interlacing of filaments to form a mesh structure. Inthe textile and other industries, these terms may have different or morespecific meanings depending on the product or application such aswhether an article is made in a sheet or cylindrical form. For purposesof the present disclosure, these terms are used interchangeably.

For some embodiments, three factors may be critical for a woven orbraided wire occlusion device for treatment of a patient's vasculaturethat can achieve a desired clinical outcome in the endovasculartreatment of cerebral aneurysms. We have found that for effective use insome applications, it may be desirable for the implant device to havesufficient radial stiffness for stability, limited pore size fornear-complete acute (intra-procedural) occlusion and a collapsed profilewhich is small enough to allow insertion through an inner lumen of amicrocatheter. A device with a radial stiffness below a certainthreshold may be unstable and may be at higher risk of embolization insome cases. Larger pores between filament intersections in a braided orwoven structure may not generate thrombus and occlude a vascular defectin an acute setting and thus may not give a treating physician or healthprofessional such clinical feedback that the flow disruption will leadto a complete and lasting occlusion of the vascular defect beingtreated. Delivery of a device for treatment of a patient's vasculaturethrough a standard microcatheter may be highly desirable to allow accessthrough the tortuous cerebral vasculature in the manner that a treatingphysician is accustomed. A detailed discussion of radial stiffness, poresize, and the necessary collapsed profile can be found in US2017/0095254, which was previously expressly incorporated by referencein its entirety.

As has been discussed, some embodiments of devices for treatment of apatient's vasculature call for sizing the device which approximates (orwith some over-sizing) the vascular site dimensions to fill the vascularsite. One might assume that scaling of a device to larger dimensions andusing larger filaments would suffice for such larger embodiments of adevice. However, for the treatment of brain aneurysms, the diameter orprofile of the radially collapsed device is limited by the cathetersizes that can be effectively navigated within the small, tortuousvessels of the brain. Further, as a device is made larger with a givenor fixed number of resilient filaments having a given size or thickness,the pores or openings between junctions of the filaments arecorrespondingly larger. In addition, for a given filament size theflexural modulus or stiffness of the filaments and thus the structuredecrease with increasing device dimension. Flexural modulus may bedefined as the ratio of stress to strain. Thus, a device may beconsidered to have a high flexural modulus or be stiff if the strain(deflection) is low under a given force. A stiff device may also be saidto have low compliance.

To properly configure larger size devices for treatment of a patient'svasculature, it may be useful to model the force on a device when thedevice is deployed into a vascular site or defect, such as a bloodvessel or aneurysm, that has a diameter or transverse dimension that issmaller than a nominal diameter or transverse dimension of the device ina relaxed unconstrained state. As discussed, it may be advisable to“over-size” the device in some cases so that there is a residual forcebetween an outside surface of the device and an inside surface of thevascular wall. The inward radial force on a device 10 that results fromover-sizing is illustrated schematically in FIG. 1 with the arrows 12 inthe figure representing the inward radial force. As shown in FIG. 2,these compressive forces on the filaments 14 of the device in FIG. 1 canbe modeled as a simply supported beam 16 with a distributed load orforce as show by the arrows 18 in the figure. It can be seen from theequation below for the deflection of a beam with two simple supports 20and a distributed load that the deflection is a function of the length,L to the 4^(th) power:Deflection of Beam=5FL⁴/384E1

-   -   where F=force,    -   L=length of beam,    -   E=Young's Modulus, and    -   1=moment of inertia.

Thus, as the size of the device increases and L increases, thecompliance increases substantially. Accordingly, an outward radial forceexerted by an outside surface of the filaments 14 of the device 10against a constraining force when inserted into a vascular site such asblood vessel or aneurysm is lower for a given amount of devicecompression or over-sizing. This force may be important in someapplications to assure device stability and to reduce the risk ofmigration of the device and potential distal embolization.

In some embodiments, a combination of small and large filament sizes maybe utilized to make a device with a desired radial compliance and yethave a collapsed profile which is configured to fit through an innerlumen of commonly used microcatheters. A device fabricated with even asmall number of relatively large filaments 14 can provide reduced radialcompliance (or increased stiffness) compared to a device made with allsmall filaments. Even a relatively small number of larger filaments mayprovide a substantial increase in bending stiffness due to change in themoment of Inertia that results from an increase in diameter withoutincreasing the total cross sectional area of the filaments. The momentof inertia (I) of a round wire or filament may be defined by theequation:I=πd ⁴/64

-   -   where d is the diameter of the wire or filament.

Since the moment of inertia is a function of filament diameter to thefourth power, a small change in the diameter greatly increases themoment of inertia. Thus, small changes in filament size can havesubstantial impact on the deflection at a given load and thus thecompliance of the device.

Thus, the stiffness can be increased by a significant amount without alarge increase in the cross sectional area of a collapsed profile of thedevice 10. This may be particularly important as device embodiments aremade larger to treat large aneurysms. While large cerebral aneurysms maybe relatively rare, they present an important therapeutic challenge assome embolic devices currently available to physicians have relativelypoor results compared to smaller aneurysms.

As such, some embodiments of devices for treatment of a patient'svasculature may be formed using a combination of filaments 14 with anumber of different diameters such as 2, 3, 4, 5 or more differentdiameters or transverse dimensions. In device embodiments wherefilaments with two different diameters are used, some larger filamentembodiments may have a transverse dimension of about 0.001 inches toabout 0.004 inches and some small filament embodiments may have atransverse dimension or diameter of about 0.0004 inches and about 0.0015inches, more specifically, about 0.0004 inches to about 0.001 inches.The ratio of the number of large filaments to the number of smallfilaments may be between about 2 and 12 and may also be between about 4and 8. In some embodiments, the difference in diameter or transversedimension between the larger and smaller filaments may be less thanabout 0.004 inches, more specifically, less than about 0.0035 inches,and even more specifically, less than about 0.002 inches.

As discussed above, device embodiments 10 for treatment of a patient'svasculature may include a plurality of wires, fibers, threads, tubes orother filamentary elements that form a structure that serves as apermeable shell. For some embodiments, a globular shape may be formedfrom such filaments by connecting or securing the ends of a tubularbraided structure. For such embodiments, the density of a braided orwoven structure may inherently increase at or near the ends where thewires or filaments 14 are brought together and decrease at or near amiddle portion 30 disposed between a proximal end 32 and distal end 34of the permeable shell 40. For some embodiments, an end or any othersuitable portion of a permeable shell 40 may be positioned in an openingor neck of a vascular defect such as an aneurysm for treatment. As such,a braided or woven filamentary device with a permeable shell may notrequire the addition of a separate defect spanning structure havingproperties different from that of a nominal portion of the permeableshell to achieve hemostasis and occlusion of the vascular defect. Such afilamentary device may be fabricated by braiding, weaving or othersuitable filament fabrication techniques. Such device embodiments may beshape set into a variety of three-dimensional shapes such as discussedherein.

Referring to FIGS. 3-10, an embodiment of a device for treatment of apatient's vasculature 10 is shown. The device 10 includes aself-expanding resilient permeable shell 40 having a proximal end 32, adistal end 34, a longitudinal axis 46 and further comprising a pluralityof elongate resilient filaments 14 including large filaments 48 andsmall filaments 50 of at least two different transverse dimensions asshown in more detail in FIGS. 5, 7, and 8. The filaments 14 have a wovenstructure and are secured relative to each other at proximal ends 60 anddistal ends 62 thereof. The permeable shell 40 of the device has aradially constrained elongated state configured for delivery within amicrocatheter 61, as shown in FIG. 11, with the thin woven filaments 14extending longitudinally from the proximal end 42 to the distal end 44radially adjacent each other along a length of the filaments.

As shown in FIGS. 3-6, the permeable shell 40 also has an expandedrelaxed state with a globular and longitudinally shortened configurationrelative to the radially constrained state. In the expanded state, thewoven filaments 14 form the self-expanding resilient permeable shell 40in a smooth path radially expanded from a longitudinal axis 46 of thedevice between the proximal end 32 and distal end 34. The wovenstructure of the filaments 14 includes a plurality of openings 64 in thepermeable shell 40 formed between the woven filaments. For someembodiments, the largest of said openings 64 may be configured to allowblood flow through the openings only at a velocity below a thromboticthreshold velocity. Thrombotic threshold velocity has been defined, atleast by some, as the time-average velocity at which more than 50% of avascular graft surface is covered by thrombus when deployed within apatient's vasculature. In the context of aneurysm occlusion, a slightlydifferent threshold may be appropriate. Accordingly, the thromboticthreshold velocity as used herein shall include the velocity at whichclotting occurs within or on a device, such as device 10, deployedwithin a patient's vasculature such that blood flow into a vasculardefect treated by the device is substantially blocked in less than about1 hour or otherwise during the treatment procedure. The blockage ofblood flow into the vascular defect may be indicated in some cases byminimal contrast agent entering the vascular defect after a sufficientamount of contrast agent has been injected into the patient'svasculature upstream of the implant site and visualized as it dissipatesfrom that site. Such sustained blockage of flow within less than about 1hour or during the duration of the implantation procedure may also bereferred to as acute occlusion of the vascular defect.

As such, once the device 10 is deployed, any blood flowing through thepermeable shell may be slowed to a velocity below the thromboticthreshold velocity and thrombus will begin to form on and around theopenings in the permeable shell 40. Ultimately, this process may beconfigured to produce acute occlusion of the vascular defect withinwhich the device 10 is deployed. For some embodiments, at least thedistal end of the permeable shell 40 may have a reverse bend in aneverted configuration such that the secured distal ends 62 of thefilaments 14 are withdrawn axially within the nominal permeable shellstructure or contour in the expanded state. For some embodiments, theproximal end of the permeable shell further includes a reverse bend inan everted configuration such that the secured proximal ends 60 of thefilaments 14 are withdrawn axially within the nominal permeable shellstructure 40 in the expanded state. As used herein, the term everted mayinclude a structure that is everted, partially everted and/or recessedwith a reverse bend as shown in the device embodiment of FIGS. 3-6. Forsuch embodiments, the ends 60 and 62 of the filaments 14 of thepermeable shell or hub structure disposed around the ends may bewithdrawn within or below the globular shaped periphery of the permeableshell of the device.

The elongate resilient filaments 14 of the permeable shell 40 may besecured relative to each other at proximal ends 60 and distal ends 62thereof by one or more methods including welding, soldering, adhesivebonding, epoxy bonding or the like. In addition to the ends of thefilaments being secured together, a distal hub 66 may also be secured tothe distal ends 62 of the thin filaments 14 of the permeable shell 40and a proximal hub 68 secured to the proximal ends 60 of the thinfilaments 14 of the permeable shell 40. The proximal hub 68 may includea cylindrical member that extends proximally beyond the proximal ends 60of the thin filaments so as to form a cavity 70 within a proximalportion of the proximal hub 68. The proximal cavity 70 may be used forholding adhesives such as epoxy, solder or any other suitable bondingagent for securing an elongate detachment tether 72 that may in turn bedetachably secured to a delivery apparatus such as is shown in FIG. 11.

For some embodiments, the elongate resilient filaments 14 of thepermeable shell 40 may have a transverse cross section that issubstantially round in shape and be made from a superelastic materialthat may also be a shape memory metal. The shape memory metal of thefilaments of the permeable shell 40 may be heat set in the globularconfiguration of the relaxed expanded state as shown in FIGS. 3-6.Suitable superelastic shape memory metals may include alloys such asNiTi alloy and the like. The superelastic properties of such alloys maybe useful in providing the resilient properties to the elongatefilaments 14 so that they can be heat set in the globular form shown,fully constrained for delivery within an inner lumen of a microcatheterand then released to self expand back to substantially the original heatset shape of the globular configuration upon deployment within apatient's body.

The device 10 may have an everted filamentary structure with a permeableshell 40 having a proximal end 32 and a distal end 34 in an expandedrelaxed state. The permeable shell 40 has a substantially enclosedconfiguration for the embodiments shown. Some or all of the permeableshell 40 of the device 10 may be configured to substantially block orimpede fluid flow or pressure into a vascular defect or otherwiseisolate the vascular defect over some period of time after the device isdeployed in an expanded state. The permeable shell 40 and device 10generally also has a low profile, radially constrained state, as shownin FIG. 11, with an elongated tubular or cylindrical configuration thatincludes the proximal end 32, the distal end 34 and a longitudinal axis46. While in the radially constrained state, the elongate flexiblefilaments 14 of the permeable shell 40 may be disposed substantiallyparallel and in close lateral proximity to each other between theproximal end and distal end forming a substantially tubular orcompressed cylindrical configuration.

Proximal ends 60 of at least some of the filaments 14 of the permeableshell 40 may be secured to the proximal hub 68 and distal ends 62 of atleast some of the filaments 14 of the permeable shell 40 are secured tothe distal hub 66, with the proximal hub 68 and distal hub 66 beingdisposed substantially concentric to the longitudinal axis 46 as shownin FIG. 4. The ends of the filaments 14 may be secured to the respectivehubs 66 and 68 by any of the methods discussed above with respect tosecurement of the filament ends to each other, including the use ofadhesives, solder, welding and the like. A middle portion 30 of thepermeable shell 40 may have a first transverse dimension with a lowprofile suitable for delivery from a microcatheter as shown in FIG. 11.Radial constraint on the device 10 may be applied by an inside surfaceof the inner lumen of a microcatheter, such as the distal end portion ofthe microcatheter 61 shown, or it may be applied by any other suitablemechanism that may be released in a controllable manner upon ejection ofthe device 10 from the distal end of the catheter. In FIG. 11 a proximalend or hub 68 of the device 10 is secured to a distal end of an elongatedelivery apparatus 111 of a delivery system 112 disposed at the proximalhub 68 of the device 10. Additional details of delivery devices can befound in, e.g., US 2016/0367260, which was previously incorporated byreference in its entirety.

Some device embodiments 10 having a braided or woven filamentarystructure may be formed using about 10 filaments to about 300 filaments14, more specifically, about 10 filaments to about 100 filaments 14, andeven more specifically, about 60 filaments to about 80 filaments 14.Some embodiments of a permeable shell 40 may include about 70 filamentsto about 300 filaments extending from the proximal end 32 to the distalend 34, more specifically, about 100 filaments to about 200 filamentsextending from the proximal end 32 to the distal end 34. For someembodiments, the filaments 14 may have a transverse dimension ordiameter of about 0.0008 inches to about 0.004 inches. The elongateresilient filaments 14 in some cases may have an outer transversedimension or diameter of about 0.0005 inch to about 0.005 inch, morespecifically, about 0.001 inch to about 0.003 inch, and in some casesabout 0.0004 inches to about 0.002 inches. For some device embodiments10 that include filaments 14 of different sizes, the large filaments 48of the permeable shell 40 may have a transverse dimension or diameterthat is about 0.001 inches to about 0.004 inches and the small filaments50 may have a transverse dimension or diameter of about 0.0004 inches toabout 0.0015 inches, more specifically, about 0.0004 inches to about0.001 inches. In addition, a difference in transverse dimension ordiameter between the small filaments 50 and the large filaments 48 maybe less than about 0.004 inches, more specifically, less than about0.0035 inches, and even more specifically, less than about 0.002 inches.For embodiments of permeable shells 40 that include filaments 14 ofdifferent sizes, the number of small filaments 50 of the permeable shell40 relative to the number of large filaments 48 of the permeable shell40 may be about 2 to 1 to about 15 to 1, more specifically, about 2 to 1to about 12 to 1, and even more specifically, about 4 to 1 to about 8 to1.

The expanded relaxed state of the permeable shell 40, as shown in FIG.4, has an axially shortened configuration relative to the constrainedstate such that the proximal hub 68 is disposed closer to the distal hub66 than in the constrained state. Both hubs 66 and 68 are disposedsubstantially concentric to the longitudinal axis 46 of the device andeach filamentary element 14 forms a smooth arc between the proximal anddistal hubs 66 and 68 with a reverse bend at each end. A longitudinalspacing between the proximal and distal hubs 66 and 68 of the permeableshell 40 in a deployed relaxed state may be about 25 percent to about 75percent of the longitudinal spacing between the proximal and distal hubs66 and 68 in the constrained cylindrical state, for some embodiments.The arc of the filaments 14 between the proximal and distal ends 32 and34 may be configured such that a middle portion of each filament 14 hasa second transverse dimension substantially greater than the firsttransverse dimension.

For some embodiments, the permeable shell 40 may have a first transversedimension in a collapsed radially constrained state of about 0.2 mm toabout 2 mm and a second transverse dimension in a relaxed expanded stateof about 4 mm to about 30 mm. For some embodiments, the secondtransverse dimension of the permeable shell 40 in an expanded state maybe about 2 times to about 150 times the first transverse dimension, morespecifically, about 10 times to about 25 times the first or constrainedtransverse dimension. A longitudinal spacing between the proximal end 32and distal end 34 of the permeable shell 40 in the relaxed expandedstate may be about 25% percent to about 75% percent of the spacingbetween the proximal end 32 and distal end 34 in the constrainedcylindrical state. For some embodiments, a major transverse dimension ofthe permeable shell 40 in a relaxed expanded state may be about 4 mm toabout 30 mm, more specifically, about 9 mm to about 15 mm, and even morespecifically, about 4 mm to about 8 mm.

An arced portion of the filaments 14 of the permeable shell 40 may havea sinusoidal-like shape with a first or outer radius 88 and a second orinner radius 90 near the ends of the permeable shell 40 as shown in FIG.6. This sinusoid-like or multiple curve shape may provide a concavity inthe proximal end 32 that may reduce an obstruction of flow in a parentvessel adjacent a vascular defect. For some embodiments, the firstradius 88 and second radius 90 of the permeable shell 40 may be betweenabout 0.12 mm to about 3 mm. For some embodiments, the distance betweenthe proximal end 32 and distal end 34 may be less than about 60% of theoverall length of the permeable shell 40 for some embodiments. Such aconfiguration may allow for the distal end 34 to flex downward towardthe proximal end 32 when the device 10 meets resistance at the distalend 34 and thus may provide longitudinal conformance. The filaments 14may be shaped in some embodiments such that there are no portions thatare without curvature over a distance of more than about 2 mm. Thus, forsome embodiments, each filament 14 may have a substantially continuouscurvature. This substantially continuous curvature may provide smoothdeployment and may reduce the risk of vessel perforation. For someembodiments, one of the ends 32 or 34 may be retracted or everted to agreater extent than the other so as to be more longitudinally or axiallyconformal than the other end.

The first radius 88 and second radius 90 of the permeable shell 40 maybe between about 0.12 mm to about 3 mm for some embodiments. For someembodiments, the distance between the proximal end 32 and distal end 34may be more than about 60% of the overall length of the expandedpermeable shell 40. Thus, the largest longitudinal distance between theinner surfaces may be about 60% to about 90% of the longitudinal lengthof the outer surfaces or the overall length of device 10. A gap betweenthe hubs 66 and 68 at the proximal end 32 and distal end 34 may allowfor the distal hub 66 to flex downward toward the proximal hub 68 whenthe device 10 meets resistance at the distal end and thus provideslongitudinal conformance. The filaments 14 may be shaped such that thereare no portions that are without curvature over a distance of more thanabout 2 mm. Thus, for some embodiments, each filament 14 may have asubstantially continuous curvature. This substantially continuouscurvature may provide smooth deployment and may reduce the risk ofvessel perforation. The distal end 34 may be retracted or everted to agreater extent than the proximal end 32 such that the distal end portionof the permeable shell 40 may be more radially conformal than theproximal end portion. Conformability of a distal end portion may providebetter device conformance to irregular shaped aneurysms or othervascular defects. A convex surface of the device may flex inward forminga concave surface to conform to curvature of a vascular site.

FIG. 10 shows an enlarged view of the filaments 14 disposed within aproximal hub 68 of the device 10 with the filaments 14 of two differentsizes constrained and tightly packed by an outer ring of the proximalhub 68. The tether member 72 may optionally be disposed within a middleportion of the filaments 14 or within the cavity 70 of the proximal hub68 proximal of the proximal ends 60 of the filaments 14 as shown in FIG.6. The distal end of the tether 72 may be secured with a knot 92 formedin the distal end thereof which is mechanically captured in the cavity70 of the proximal hub 68 formed by a proximal shoulder portion 94 ofthe proximal hub 68. The knotted distal end 92 of the tether 72 may alsobe secured by bonding or potting of the distal end of the tether 72within the cavity 70 and optionally amongst the proximal ends 60 of thefilaments 14 with mechanical compression, adhesive bonding, welding,soldering, brazing or the like. The tether embodiment 72 shown in FIG. 6has a knotted distal end 92 potted in the cavity of the proximal hub 68with an adhesive. Such a tether 72 may be a dissolvable, severable orreleasable tether that may be part of a delivery apparatus 111 used todeploy the device 10 as shown in FIG. 11 and FIGS. 23-26. FIG. 10 alsoshows the large filaments 48 and small filaments 50 disposed within andconstrained by the proximal hub 68 which may be configured to secure thelarge and small filaments 48 and 50 in place relative to each otherwithin the outer ring of the proximal hub 68.

FIGS. 7 and 8 illustrate some configuration embodiments of braidedfilaments 14 of a permeable shell 40 of the device 10 for treatment of apatient's vasculature. The braid structure in each embodiment is shownwith a circular shape 100 disposed within a pore 64 of a woven orbraided structure with the circular shape 100 making contact with eachadjacent filament segment. The pore opening size may be determined atleast in part by the size of the filament elements 14 of the braid, theangle overlapping filaments make relative to each other and the picksper inch of the braid structure. For some embodiments, the cells oropenings 64 may have an elongated substantially diamond shape as shownin FIG. 7, and the pores or openings 64 of the permeable shell 40 mayhave a substantially more square shape toward a middle portion 30 of thedevice 10, as shown in FIG. 8. The diamond shaped pores or openings 64may have a length substantially greater than the width particularly nearthe hubs 66 and 68. In some embodiments, the ratio of diamond shapedpore or opening length to width may exceed a ratio of 3 to 1 for somecells. The diamond-shaped openings 64 may have lengths greater than thewidth thus having an aspect ratio, defined as Length/Width of greaterthan 1. The openings 64 near the hubs 66 and 68 may have substantiallylarger aspect ratios than those farther from the hubs as shown in FIG.7. The aspect ratio of openings 64 adjacent the hubs may be greater thanabout 4 to 1. The aspect ratio of openings 64 near the largest diametermay be between about 0.75 to 1 and about 2 to 1 for some embodiments.For some embodiments, the aspect ratio of the openings 64 in thepermeable shell 40 may be about 0.5 to 1 to about 2 to 1.

The pore size defined by the largest circular shapes 100 that may bedisposed within openings 64 of the braided structure of the permeableshell 40 without displacing or distorting the filaments 14 surroundingthe opening 64 may range in size from about 0.005 inches to about 0.01inches, more specifically, about 0.006 inches to about 0.009 inches,even more specifically, about 0.007 inches to about 0.008 inches forsome embodiments. In addition, at least some of the openings 64 formedbetween adjacent filaments 14 of the permeable shell 40 of the device 10may be configured to allow blood flow through the openings 64 only at avelocity below a thrombotic threshold velocity. For some embodiments,the largest openings 64 in the permeable shell structure 40 may beconfigured to allow blood flow through the openings 64 only at avelocity below a thrombotic threshold velocity. As discussed above, thepore size may be less than about 0.016 inches, more specifically, lessthan about 0.012 inches for some embodiments. For some embodiments, theopenings 64 formed between adjacent filaments 14 may be about 0.005inches to about 0.04 inches.

FIG. 12 illustrates in transverse cross section an embodiment of aproximal hub 68 showing the configuration of filaments which may betightly packed and radially constrained by an inside surface of theproximal hub 68. In some embodiments, the braided or woven structure ofthe permeable shell 40 formed from such filaments 14 may be constructedusing a large number of small filaments. The number of filaments 14 maybe greater than 125 and may also be between about 80 filaments and about180 filaments. As discussed above, the total number of filaments 14 forsome embodiments may be about 70 filaments to about 300 filaments, morespecifically, about 100 filaments to about 200 filaments. In someembodiments, the braided structure of the permeable shell 40 may beconstructed with two or more sizes of filaments 14. For example, thestructure may have several larger filaments that provide structuralsupport and several smaller filaments that provide the desired pore sizeand density and thus flow resistance to achieve a thrombotic thresholdvelocity in some cases. For some embodiments, small filaments 50 of thepermeable shell 40 may have a transverse dimension or diameter of about0.0006 inches to about 0.002 inches for some embodiments and about0.0004 inches to about 0.001 inches in other embodiments. The largefilaments 48 may have a transverse dimension or diameter of about 0.0015inches to about 0.004 inches in some embodiments and about 0.001 inchesto about 0.004 inches in other embodiments. The filaments 14 may bebraided in a plain weave that is one under, one over structure (shown inFIGS. 7 and 8) or a supplementary weave; more than one warp interlacewith one or more than one weft. The pick count may be varied betweenabout 25 and 200 picks per inch (PPI).

Intrasaccular occlusive devices, such as the one shown in FIG. 13, cansometimes utilize an apple-core braid winding shape, where a proximal137 a and/or distal stem 137 b are include at or near the proximal 132and distal 134 ends of device 110. The proximal stem 137 a representsthe attachment junction with a mechanical pusher device used to placethe device 110.

In some embodiments, a hub (sometimes configured as a tubular markerband) is used within this region as an attachment junction for all theassociated wires comprising the device—meaning the various wirescomprising the intrasaccular device may proximally terminate at the hubinterface, as shown and described with respect to earlier embodiments(e.g., FIG. 6). One advantage of a tubular marker band (e.g. made of aradiopaque material such as tantalum, gold, platinum, or palladium) isenhanced visualization of the ends of the device when radiographicimaging is used. The wires can terminate/mate to an external surface ofthe hub, or along an internal lumen of the hub. The tubular marker bandmay sit over a terminal portion of the stem 137 a or 137 b. In someembodiments, as shown, (e.g., in FIG. 6) the hub/tubular marker does notextend proximally or distally beyond the length of the device itself. Inother embodiments, the hub/tubular marker does extend proximally and/ordistally beyond the length of the device such that it juts outproximally and/or distally beyond the rest of the mesh occlusivedevice—meaning the hub/tubular marker may extend proximally past a planedefined by the proximal most edge of the expanded state of the permeableshell 140, and distally beyond a plane defined by the distal most edgeof the expanded state of the permeable shell 140.

The proximal stem 137 a can sit within a proximal dimpled, recessed, orconcave section 133. Often this proximal dimpled, recessed, or concavesection 133 helps ensure the device 110 can sit within the target regionwhile also occluding the target region. In some circumstances, theproximal stem 137 a may jut out of the treatment site (e.g., aneurysm)and into the parent vessel when implanted due to various reasons. Somereasons may include the dimensions of the associated treatment site inwhich the device is occluding (e.g., the sizing of the device relativeto the aneurysm), and/or the proximal neck opening of the aneurysm.

Generally, with intrasaccular occlusion devices or intrasaccular flowdisruption devices, it is desirable to have a significantflow-disruption effect at the proximal end of the device to reduce theblood flow at the neck region—in turn, thereby reducing blood flow inthe aneurysm. The mesh of braided wires forming the proximal dimpledregion 133 of the device (the portion typically overlying the neck ofthe aneurysm) helps provide this flow-disruption effect.Intra-aneurysmal flow stagnation resulting from the flow disruptioneffect promotes thrombosis within the aneurysm and subsequentobliteration of the aneurysm over time.

Embodiments of this device augment flow-disruption at the proximal endof the device by providing an additional layer or permeable shell thatcan fill the proximal dimple, recessed, or concave section 133 locatedat a proximal region of the intrasaccular device. In some cases, theseembodiments can facilitate easier placement of an intrasaccular devicewithin a sidewall aneurysm.

An intrasaccular occlusive device 210 is shown in FIGS. 14-15. Thedevice 210 includes an intrasaccular device portion 240 having aproximal recess 133 and a distal recess 135, similar to the embodimentsdescribed above. Furthermore, distal stem 137 b and proximal stem 237 aare utilized in each proximal recess 133 and distal recess 135 region.Distal stem 137 b is configured similar to the other embodiments, wherea tubular hub or marker band (not shown) can be used along the distalend of the stem (e.g., as a distal terminus for the braided implantwires). A proximal stem 237 a is also used. In one embodiment, as shownin FIGS. 14-15, the proximal stem 237 a is shorter than the proximalstem 137 a of FIG. 13 and sits completely within the proximal dimpled orconcave section 133. The proximal stem 237 a is connected to a secondocclusive element 222.

Going further into the details of the intrasaccular device 210, device210 includes two interconnected braided structures 240 and 222, whichcombine to form a barrel-like or globular-like structure. The overallocclusive device 210 will comprise the first (distally-oriented)occlusive element 240 and the second (proximally-oriented) occlusiveelement 222.

FIG. 15 shows a deployment configuration, whereby occlusive element 222is in an elongated configuration. A proximal end of the occlusiveelement 222 is connected to a delivery pusher 243 (e.g., through atubular hub or marker band 252 a), whereby the delivery pusher 243 isused to navigate device 210 (which includes intrasaccular portion 240and second occlusive portion 222).

In a first delivery configuration, the occlusive element 222 adopts theelongated configuration shown in FIG. 15. In a delivered configuration,shown in FIG. 14, the occlusive element 222 adopts a radially expansileand longitudinally compressed configuration—whereby occlusive element222 sits flush within the proximal dimple, recessed, or concave section133 of the device 210 in a fully deployed configuration, thereby sealingthe neck of the aneurysm/treatment site. The inclusion of the occlusiveelement 222, which can span the proximal recessed section 133 of device210, augments the flow disruption effect at the proximal end (whichspans the neck region of the aneurysm) of the device 210, due to theadditional barrier to blood entry provided by this portion 222. By wayof example, blood flowing into the neck region of the aneurysm wouldhave to first pass by the wires of the occlusive portion 222, then thewires of the intrasaccular device portion 240. In this way, there isincreased resistance to blood flow along the proximal, or neck-facingregion of the device 210—thereby augmenting flow disruption at theproximal end of the device.

In one embodiment, both occlusive elements 240, 222 are created fromwires made from a shape-memory alloy, such as nitinol wires and/or DFT(drawn filled tubes) and heat set into the shapes shown in FIG. 14. Inone example, where DFT is used, the DFT is composed of a radiopaque(e.g., tantalum, platinum, gold, or palladium) core surrounded by anitinol jacket. In one embodiment, only nitinol wires are used forocclusive elements 240, 222. In another embodiment, only DFT wires areused for occlusive elements 240, 222. In another embodiment, a mixtureof nitinol and DFT wires are used along one or both of occlusiveelements 240, 222 (e.g., where one is solely composed of nitinol and theother solely composed of DFT, or where one or both are composed of amixture of DFT and nitinol wires).

In one example, the first occlusive element 240 is manufactured and heatset into the barrel-like structure having proximal 133 and distal 135dimpled concave sections. The second occlusive element 222 is thenmanufactured and heat set such that the distally-facing (or upwardfacing, in the context of FIGS. 14-15) outer surface of the secondocclusive element 222 is configured to conform or mate with theproximally-facing (or downward facing, in the context of the samefigures) surface of the proximal dimpled region 133. The secondocclusive element 222 is configured to adopt a convex shape that mateswith the concave shape of the proximal dimpled section 133 whenimplanted. The two occlusive elements 240, 222 may be connected, forinstance by a hub or marker band element. In alternative configurations,the first and second occlusive elements 240, 222 are made from the sametubular mesh (same woven filaments), where the second occlusive elementis formed of wires which are tracked through the narrow diameterproximal stem region and then wound into the dimpled region of the firstocclusive element. The device can be manufactured by wrapping a singletubular mesh around a fixture containing the shape of occlusive elements240, 222. The fixture and the braided mesh can then be heat set toobtain the secondary shape memory. Thus, the first and second occlusiveelements can either be completely separate mesh braids or can be formedfrom the same mesh braid wound in a particular configuration. Proximalhub or marker band 252 a (and a distal hub or marker band, not shown)can then be attached to the device, respectively, at the proximal anddistal ends. The proximal hub or marker band 252 a can then be attachedto a pusher 243.

In some configurations, a hub or marker band can be placed betweenocclusive element 222 and occlusive element 240. Where both elements arecomposed of the same wires, the wires are passed through a hub or markerband and then continue into the second occlusive element. Alternatively,where both elements are composed of the same wires, no hub or markerband is used and, instead, the wires simply extend from a distal end orregion of occlusive portion 240, through stem 237 a, to the proximal endor region of occlusive portion 222. A device in which there is no hub ormarker band between the first and second occlusive elements 240, 222 maybe less stiff than an embodiment including a hub or marker band.

Where occlusive elements 240 and 222 are composed of different/separatewire braids, then a hub or marker band can be used between these twosections (e.g., along proximal stem 237 a) where the wires of occlusiveelement 240 terminate along an external or internal surface of the hubor marker band, and the separate wires of occlusive element 222 thenbegin along an external or internal surface of the same hub or markerband. Alternatively, the wires of occlusive element 240 proximallyterminate at a first hub or marker band and the separate wires ofocclusive element 222 begin at an adjacent hub or hub or marker band.

The second occlusive element 222, which bridges the space in theproximal dimpled or concave section 133 of the first occlusive element240, has good shape retention properties that enable it to fit into thedimpled recessed shape of proximal dimpled region 133. Along with theprovided occlusive benefit at the neck of the treatment site/aneurysm,the second occlusive element 222 also provides additional push strengthas a bridge between the proximal mechanical pusher 243 and the distalfirst occlusive element, thereby providing more control duringdeployment.

FIG. 15 illustrates a configuration of the device when it is beingdelivered. The first occlusive element 240 adopts its heat seat,expanded configuration when freed from a delivery catheter (not shown).The proximal end of the first occlusive element 240 is connected to adistal end of the second occlusive element 222 through proximal stem orelongate proximal extension 237 a, which acts as a flexible jointallowing the first occlusive element 240 to pivot or flex relative tothe second occlusive element 222. Upon delivery, the user distallyadvances the pusher 243 so that the proximal occlusive element 222 ispushed into recess 133 to occupy the space of the recess—such that theconfiguration in FIG. 14 is adopted. The pusher is then detached fromthe device 210 so that the device 210 remains as an implant.

As seen in FIGS. 16A-16E, the device 210 contains a braided region thatacts as a flexible joint 237 a between the first 240 and second 222occlusive elements. The device 210 is delivered using a microcatheter 61and pusher 243, which is connected to a proximal end of the device 210.When delivery is attempted to an aneurysm, e.g., a sidewall aneurysm,the flexible joint between the first 240 and second 222 occlusiveelements allows for easier delivery because the first occlusive element240 is capable of deflecting or pivoting relative to a longitudinal axisformed by the pusher and the second permeable shell or a longitudinalaxis of the second permeable shell. The flexible joint 237 a between thefirst and second occlusive elements allows for the first occlusiveelement 240 to deflect, bend, or flex at an angle of up to about 180°,alternatively up to about 150°, alternatively up to about 120°,alternatively up to about 90°, alternatively up to about 60°,alternatively up to about 45°, alternatively up to about 30°,alternatively up to about 10°. The second occlusive element 222 willgenerally adopt a more elongated shape during delivery, e.g., while inthe microcatheter. After release from the lumen of the microcatheter butbefore placement within the proximal concave section of the firstocclusive element 240, the second occlusive element 222 will adopt afirst expanded state while the second occlusive element is under tensionfrom a proximal direction. The first expanded state has a longer lengthand smaller radius than the second expanded state that the secondocclusive element adopts after the proximal tension is released or aforce is applied to push it against the proximal end of the firstpermeable shell. Upon placement within the aneurysm and release of theproximal tension, the second occlusive element 222 will abut the firstocclusive element 240 within the proximal dimpled concave region 133 andassume the second expanded state, which is configured to sit within theproximal dimpled concave region 133. The deployment of device 210 withthe second occlusive element 222 seated in the proximal dimpled concaveregion 133 assists in occluding blood flow at the proximal end of thedevice 210 and forming a strong proximal occlusive barrier to bloodflow. The second occlusive element 222 will be heat set into a convexshape that generally fills the proximal concave section. Thus, it willreadily adopt this convex shape that mates with the dimpled concaveshape of the proximal region of the first occlusive device 210. The userwill then detach the pusher 243 from the proximal end of the secondocclusive element 222, thereby leaving the occlusive implant 210 withinthe target treatment region (e.g., an aneurysm 160).

The second occlusive device 222, along with providing increasedresistance to blood flow at the neck of the aneurysm by filling in therecess 133, can also help pivot the connected occlusive portion 240 intoa proper orientation after deployment into the treatment site. Asdiscussed above, intrasaccular devices can be optimal treatments forbifurcation aneurysms where a catheter can be delivered directly from aparent artery into the aneurysm at a vessel bifurcation junction. Thisis more complicated for sidewall aneurysms, where the catheter oftencomes into the aneurysm at an odd, non-linear angle. As such, theintrasaccular device may be deployed at an odd angle, and closer to oneside of the aneurysm rather than directly in the middle. This odddelivery angle can negatively affect flow disruption at the neck of theaneurysm, which can contribute to the intrasaccular device shiftingwithin the aneurysm over time. Sidewall aneurysms also can beirregularly shaped, further making proper entry and seating of theintrasaccular device in the aneurysm difficult. Because the secondocclusive device 222 is proximally oriented with respect to the primaryocclusive portion 240, during implantation, the second occlusive portion222 will exert force against the distally connected occlusive portion240. This force or exertion can help orient the primary occlusiveportion 240 into a proper orientation and position in the aneurysm afterit is deployed from the delivery catheter. Depending on the angle andshape of the sidewall aneurysm, the sidewall aneurysm can be angled, forinstance at about 90 degrees or between about 60-120 degrees relative tothe parent artery. The secondary occlusive section 222 can help inarticulating or positioning the overall intrasaccular device to belocated in a proper orientation within the aneurysm. This is due to theforce provided by the proximal occlusive portion 222, as well as theflexible nature of joint/stem 237 a, as described earlier.

Though the inclusion of the second or proximal occlusive section 222offers some advantages in deployment in sidewall aneurysms, thisadditional section 222 also offers some advantages when used inbifurcation aneurysms as well. For instance, the proximal occlusivesection 222 offers additional blood disruption at the proximal sectionof the device 210 toward the neck-portion of the aneurysm, therebyreducing blood flow into the aneurysm and promoting healing over time.Additionally, the articulation described above can be used to properlyposition the intrasaccular device 210 within a bifurcation aneurysm, forexample in a particularly wide or large-necked aneurysm where it may bedifficult to otherwise seat the intrasaccular device 210 properly withregard to the neck region of the aneurysm.

In some embodiments, the first occlusive element 240 and secondocclusive element 222 comprise similar metallic wire material. In someembodiments, the first occlusive element 240 may be softer and have amore flexible configuration than the second occlusive element 222. Morestiffness may be desirable along the proximal occlusive element 222 inorder to provide enough push force against first occlusive element 240and to provide more flow resistance along the proximal section of theintrasaccular implant 210. The first occlusive element 240, forinstance, can use relatively smaller wires and/or a denser wind patternthan the second shell 222 in order to achieve this more flexibleconfiguration. In contrast, the second occlusive element 222 may bestiffer than the first shell 240. This enhanced stiffness is achieved,for instance, by use of larger sized wires which are more spread out(e.g. having a smaller pic count). The second occlusive element 222 canalso include radiopaque components, such as tantalum, to further enhancestiffness and well as to augment visualization. A good shape memorymaterial, such as nitinol and/or DFT wire, may also be used to createthe metallic mesh for the first 240 and second 222 occlusive elements.

The first occlusive element 240 may be formed by weaving or braidingbetween about 24 and 216 filaments, alternatively between about 60 and144 filaments, alternatively between about 72 and 108 filaments. Thefilaments that are woven to form the first occlusive element 240 mayhave a diameter of between about 0.0005″ and 0.002″, alternativelybetween about 0.0006″ and 0.00125″, alternatively between about 0.00075″and 0.001″. The first occlusive element 240 may have a radial stiffnessbetween about 0.014 lbf and 0.284 lbf.

The second occlusive element 222 may be formed by weaving or braidingbetween about 24 and 216 filaments, alternatively between 60 and 144filaments, alternatively between about 72 and 108 filaments. Thefilaments that are woven to form the second occlusive element 222 mayhave a diameter of between about 0.0005″ and 0.002″, alternativelybetween about 0.0006″ and 0.00125″, alternatively between about 0.00075″and 0.001″. The second occlusive element 222 may have a radial stiffnessbetween about 0.014 lbf and 0.284 lbf.

For some embodiments, the permeable shell 40, 140, 240 or portionsthereof may be porous and may be highly permeable to liquids. Incontrast to most vascular prosthesis fabrics or grafts which typicallyhave a water permeability below 2,000 ml/min/cm² when measured at apressure of 120 mmHg, the permeable shell 40 of some embodimentsdiscussed herein may have a water permeability greater than about 2,000ml/min/cm², in some cases greater than about 2,500 ml/min/cm². For someembodiments, water permeability of the permeable shell 40 or portionsthereof may be between about 2,000 and 10,000 ml/min/cm², morespecifically, about 2,000 ml/min/cm² to about 15,000 ml/min/cm², whenmeasured at a pressure of 120 mmHg.

Device embodiments and components thereof may include metals, polymers,biologic materials and composites thereof. Suitable metals includezirconium-based alloys, cobalt-chrome alloys, nickel-titanium alloys,platinum, tantalum, stainless steel, titanium, gold, and tungsten.Potentially suitable polymers include but are not limited to acrylics,silk, silicones, polyvinyl alcohol, polypropylene, polyvinyl alcohol,polyesters (e.g. polyethylene terephthalate or PET), PolyEtherEtherKetone (PEEK), polytetrafluoroethylene (PTFE), polycarbonate urethane(PCU) and polyurethane (PU). Device embodiments may include a materialthat degrades or is absorbed or eroded by the body. A bioresorbable(e.g., breaks down and is absorbed by a cell, tissue, or other mechanismwithin the body) or bioabsorbable (similar to bioresorbable) materialmay be used. Alternatively, a bioerodable (e.g., erodes or degrades overtime by contact with surrounding tissue fluids, through cellularactivity or other physiological degradation mechanisms), biodegradable(e.g., degrades over time by enzymatic or hydrolytic action, or othermechanism in the body), or dissolvable material may be employed. Each ofthese terms is interpreted to be interchangeable. bioabsorbable polymer.Potentially suitable bioabsorbable materials include polylactic acid(PLA), poly(alpha-hydroxy acid) such as poly-L-lactide (PLLA),poly-D-lactide (PDLA), polyglycolide (PGA), polydioxanone,polycaprolactone, polygluconate, polylactic acid-polyethylene oxidecopolymers, modified cellulose, collagen, poly(hydroxybutyrate),polyanhydride, polyphosphoester, poly(amino acids), or related copolymermaterials. An absorbable composite fiber may be made by combining areinforcement fiber made from a copolymer of about 18% glycolic acid andabout 82% lactic acid with a matrix material consisting of a blend ofthe above copolymer with about 20% polycaprolactone (PCL).

Permeable shell embodiments 40, 140, 240 may be formed at least in partof wire, ribbon, or other filamentary elements. These filamentaryelements 14 may have circular, elliptical, ovoid, square, rectangular,or triangular cross-sections. Permeable shell embodiments 40 may also beformed using conventional machining, laser cutting, electrical dischargemachining (EDM) or photochemical machining (PCM). If made of a metal, itmay be formed from either metallic tubes or sheet material.

Device embodiments 10, 110, 210 discussed herein may be delivered anddeployed from a delivery and positioning system 112 that includes amicrocatheter 61, such as the type of microcatheter 61 that is known inthe art of neurovascular navigation and therapy. Device embodiments fortreatment of a patient's vasculature 10, 110, 210 may be elasticallycollapsed and restrained by a tube or other radial restraint, such as aninner lumen 120 of a microcatheter 61, for delivery and deployment. Themicrocatheter 61 may generally be inserted through a small incision 152accessing a peripheral blood vessel such as the femoral artery orbrachial artery. The microcatheter 61 may be delivered or otherwisenavigated to a desired treatment site 154 from a position outside thepatient's body 156 over a guidewire 159 under fluoroscopy or by othersuitable guiding methods. The guidewire 159 may be removed during such aprocedure to allow insertion of the device 10, 110, 210 secured to adelivery apparatus 111 of the delivery system 112 through the innerlumen 120 of a microcatheter 61 in some cases. FIG. 17 illustrates aschematic view of a patient 158 undergoing treatment of a vasculardefect 160 as shown in FIG. 18. An access sheath 162 is shown disposedwithin either a radial artery 164 or femoral artery 166 of the patient158 with a delivery system 112 that includes a microcatheter 61 anddelivery apparatus 111 disposed within the access sheath 162. Thedelivery system 112 is shown extending distally into the vasculature ofthe patient's brain adjacent a vascular defect 160 in the patient'sbrain.

Access to a variety of blood vessels of a patient may be established,including arteries such as the femoral artery 166, radial artery 164,and the like in order to achieve percutaneous access to a vasculardefect 160. In general, the patient 158 may be prepared for surgery andthe access artery is exposed via a small surgical incision 152 andaccess to the lumen is gained using the Seldinger technique where anintroducing needle is used to place a wire over which a dilator orseries of dilators dilates a vessel allowing an introducer sheath 162 tobe inserted into the vessel. This would allow the device to be usedpercutaneously. With an introducer sheath 162 in place, a guidingcatheter 168 is then used to provide a safe passageway from the entrysite to a region near the target site 154 to be treated. For example, intreating a site in the human brain, a guiding catheter 168 would bechosen which would extend from the entry site 152 at the femoral arteryup through the large arteries extending around the heart through theaortic arch, and downstream through one of the arteries extending fromthe upper side of the aorta such as the carotid artery 170. Typically, aguidewire 159 and neurovascular microcatheter 61 are then placed throughthe guiding catheter 168 and advanced through the patient's vasculature,until a distal end 151 of the microcatheter 61 is disposed adjacent orwithin the target vascular defect 160, such as an aneurysm. Exemplaryguidewires 159 for neurovascular use include the Synchro2® made byBoston Scientific and the Glidewire Gold Neuro® made by MicroVentionTerumo. Typical guidewire sizes may include 0.014 inches and 0.018inches. Once the distal end 151 of the catheter 61 is positioned at thesite, often by locating its distal end through the use of radiopaquemarker material and fluoroscopy, the catheter is cleared. For example,if a guidewire 159 has been used to position the microcatheter 61, it iswithdrawn from the catheter 61 and then the implant delivery apparatus111 is advanced through the microcatheter 61.

Delivery and deployment of device embodiments 10, 110, 210 discussedherein may be carried out by first compressing the device 10, 110, 210to a radially constrained and longitudinally flexible state as shown inFIG. 11. The device 10, 110, 210 may then be delivered to a desiredtreatment site 154 while disposed within the microcatheter 61, and thenejected or otherwise deployed from a distal end 151 of the microcatheter61. In other method embodiments, the microcatheter 61 may first benavigated to a desired treatment site 154 over a guidewire 159 or byother suitable navigation techniques. The distal end of themicrocatheter 61 may be positioned such that a distal port of themicrocatheter 61 is directed towards or disposed within a vasculardefect 160 to be treated and the guidewire 159 withdrawn. The device 10,110, 210 secured to a suitable delivery apparatus 111 may then beradially constrained, inserted into a proximal portion of the innerlumen 120 of the microcatheter 61 and distally advanced to the vasculardefect 160 through the inner lumen 120.

Once disposed within the vascular defect 160, the device 10, 110, 210may then allowed to assume an expanded relaxed or partially relaxedstate with the permeable shell 40, 140, 240 of the device spanning orpartially spanning a portion of the vascular defect 160 or the entirevascular defect 160. The device 10, 110, 210 may also be activated bythe application of an energy source to assume an expanded deployedconfiguration once ejected from the distal section of the microcatheter61 for some embodiments. Once the device 10 is deployed at a desiredtreatment site 154, the microcatheter 61 may then be withdrawn.

Some embodiments of devices for the treatment of a patient's vasculature10, 110, 210 discussed herein may be directed to the treatment ofspecific types of defects of a patient's vasculature. For example,referring to FIG. 18, an aneurysm 160 commonly referred to as a terminalaneurysm is shown in section. Terminal aneurysms occur typically atbifurcations in a patient's vasculature where blood flow, indicated bythe arrows 172, from a supply vessel splits into two or more branchvessels directed away from each other. The main flow of blood from thesupply vessel 174, such as a basilar artery, sometimes impinges on thevessel where the vessel diverges and where the aneurysm sack forms.Terminal aneurysms may have a well-defined neck structure where theprofile of the aneurysm 160 narrows adjacent the nominal vessel profile,but other terminal aneurysm embodiments may have a less defined neckstructure or no neck structure. FIG. 19 illustrates a typical berry typeaneurysm 160 in section where a portion of a wall of a nominal vesselsection weakens and expands into a sack like structure ballooning awayfrom the nominal vessel surface and profile. Some berry type aneurysmsmay have a well-defined neck structure as shown in FIG. 19, but othersmay have a less defined neck structure or none at all. FIG. 19 alsoshows some optional procedures wherein a stent 173 or other type ofsupport has been deployed in the parent vessel 174 adjacent theaneurysm. Also, shown is embolic material 176 being deposited into theaneurysm 160 through a microcatheter 61. Either or both of the stent 173and embolic material 176 may be so deployed either before or after thedeployment of a device for treatment of a patient's vasculature 10.

Prior to delivery and deployment of a device for treatment of apatient's vasculature 10, 110, 210, it may be desirable for the treatingphysician to choose an appropriately sized device 10, 110, 210 tooptimize the treatment results. Some embodiments of treatment mayinclude estimating a volume of a vascular site or defect 160 to betreated and selecting a device 10, 110, 210 with a volume that issubstantially the same volume or slightly over-sized relative to thevolume of the vascular site or defect 160. The volume of the vasculardefect 160 to be occluded may be determined using three-dimensionalangiography or other similar imaging techniques along with softwarewhich calculates the volume of a selected region. The amount ofover-sizing may be between about 2% and 15% of the measured volume. Insome embodiments, such as a very irregular shaped aneurysm, it may bedesirable to under-size the volume of the device 10, 110, 210. Smalllobes or “daughter aneurysms” may be excluded from the volume, defininga truncated volume which may be only partially filled by the devicewithout affecting the outcome. A device 10, 110, 210 deployed withinsuch an irregularly shaped aneurysm 160 is shown in FIG. 28 discussedbelow. Such a method embodiment may also include implanting or deployingthe device 10, 110, 210 so that the vascular defect 160 is substantiallyfilled volumetrically by a combination of device and blood containedtherein. The device 10, 110, 210 may be configured to be sufficientlyconformal to adapt to irregular shaped vascular defects 160 so that atleast about 75%, in some cases about 80%, of the vascular defect volumeis occluded by a combination of device 10, 110, 210 and blood containedtherein.

In particular, for some treatment embodiments, it may be desirable tochoose a device 10, 110, 210 that is properly oversized in a transversedimension so as to achieve a desired conformance, radial force and fitafter deployment of the device 10. FIGS. 20-22 illustrate a schematicrepresentation of how a device 10, 110, 210 may be chosen for a properfit after deployment that is initially oversized in a transversedimension by at least about 10% of the largest transverse dimension ofthe vascular defect 160 and sometimes up to about 100% of the largesttransverse dimension. For some embodiments, the device 10, 110, 210 maybe oversized a small amount (e.g. less than about 1.5 mm) in relation tomeasured dimensions for the width, height or neck diameter of thevascular defect 160.

In FIG. 20, a vascular defect 160 in the form of a cerebral aneurysm isshown with horizontal arrows 180 and vertical arrows 182 indicating theapproximate largest interior dimensions of the defect 160. Arrow 180extending horizontally indicates the largest transverse dimension of thedefect 160. In FIG. 21, a dashed outline 184 of a device for treatmentof the vascular defect is shown superimposed over the vascular defect160 of FIG. 20 illustrating how a device 10, 110, 210 that has beenchosen to be approximately 20% oversized in a transverse dimension wouldlook in its unconstrained, relaxed state. FIG. 22 illustrates how thedevice 10, 110, 210, which is indicated by the dashed line 184 of FIG.21 might conform to the interior surface of the vascular defect 160after deployment whereby the nominal transverse dimension of the device10, 110, 210 in a relaxed unconstrained state has now been slightlyconstrained by the inward radial force 185 exerted by the vasculardefect 160 on the device 10, 110, 210. In response, as the filaments 14,114, 214 of the device 10, 110, 210 and thus the permeable shell 40,140, 240 made therefrom have a constant length, the device 10, 110, 210has assumed a slightly elongated shape in the axial or longitudinal axisof the device 10 so as to elongate and better fill the interior volumeof the defect 160 as indicated by the downward arrow 186 in FIG. 22.

Once a properly sized device 10, 110, 210 has been selected, thedelivery and deployment process may then proceed. It should also benoted also that the properties of the device embodiments 10, 110, 210and delivery system embodiments 112 discussed herein generally allow forretraction of a device 10 after initial deployment into a defect 160,but before detachment of the device 10, 110, 210. Therefore, it may alsobe possible and desirable to withdraw or retrieve an initially deployeddevice 10 after the fit within the defect 160 has been evaluated infavor of a differently sized device 10, 110, 210. An example of aterminal aneurysm 160 is shown in FIG. 23 in section. The tip 151 of acatheter, such as a microcatheter 61 may be advanced into or adjacentthe vascular site or defect 160 (e.g. aneurysm) as shown in FIG. 24. Forsome embodiments, an embolic coil or other vaso-occlusive device ormaterial 176 (as shown for example in FIG. 19) may optionally be placedwithin the aneurysm 160 to provide a framework for receiving the device10, 110, 210. In addition, a stent 173 may be placed within a parentvessel 174 of some aneurysms substantially crossing the aneurysm neckprior to or during delivery of devices for treatment of a patient'svasculature discussed herein (also as shown for example in FIG. 19). Anexample of a suitable microcatheter 61 having an inner lumen diameter ofabout 0.020 inches to about 0.022 inches is the Rapid Transit®manufactured by Cordis Corporation. Examples of some suitablemicrocatheters 61 may include microcatheters having an inner lumendiameter of about 0.026 inch to about 0.028 inch, such as the Rebar® byEv3 Company, the Renegade Hi-Flow® by Boston Scientific Corporation, andthe Mass Transit® by Cordis Corporation. Suitable microcatheters havingan inner lumen diameter of about 0.031 inch to about 0.033 inch mayinclude the Marksmen® by Chestnut Medical Technologies, Inc. and theVasco 28® by Balt Extrusion. A suitable microcatheter 61 having an innerlumen diameter of about 0.039 inch to about 0.041 inch includes theVasco 35 by Balt Extrusion. These microcatheters 61 are listed asexemplary embodiments only, other suitable microcatheters may also beused with any of the embodiments discussed herein.

Detachment of the device 10, 110, 210 from the delivery apparatus 111may be controlled by a control switch 188 disposed at a proximal end ofthe delivery system 112, which may also be coupled to an energy source142, which severs the tether 72 that secures the proximal hub 68 of thedevice 10 to the delivery apparatus 111. While disposed within themicrocatheter 61 or other suitable delivery system 112, as shown in FIG.11, the filaments 14, 114, 214 of the permeable shell 40, 140, 240 maytake on an elongated, non-everted configuration substantially parallelto each other and a longitudinal axis of the catheter 61. Once thedevice 10, 110, 210 is pushed out of the distal port of themicrocatheter 61, or the radial constraint is otherwise removed, thedistal ends 62 of the filaments 14, 114, 214 may then axially contracttowards each other so as to assume the globular everted configurationwithin the vascular defect 160 as shown in FIG. 25.

The device 10, 110, 210 may be inserted through the microcatheter 61such that the catheter lumen 120 restrains radial expansion of thedevice 10, 110, 210 during delivery. Once the distal tip or deploymentport of the delivery system 112 is positioned in a desirable locationadjacent or within a vascular defect 160, the device 10, 110, 210 may bedeployed out the distal end of the catheter 61 thus allowing the deviceto begin to radially expand as shown in FIG. 25. As the device 10, 110,210 emerges from the distal end of the delivery system 112, the device10, 110, 210 expands to an expanded state within the vascular defect160, but may be at least partially constrained by an interior surface ofthe vascular defect 160.

Upon full deployment, radial expansion of the device 10, 110, 210 mayserve to secure the device 10, 110, 210 within the vascular defect 160and also deploy the permeable shell 40 across at least a portion of anopening 190 (e.g. aneurysm neck) so as to at least partially isolate thevascular defect 160 from flow, pressure or both of the patient'svasculature adjacent the vascular defect 160 as shown in FIG. 26. Theconformability of the device 10, 110, 210, particularly in the neckregion 190 may provide for improved sealing. For some embodiments, oncedeployed, the permeable shell 40, 140, 240 may substantially slow theflow of fluids and impede flow into the vascular site and thus reducepressure within the vascular defect 160. For some embodiments, thedevice 10, 110, 210 may be implanted substantially within the vasculardefect 160, however, in some embodiments, a portion of the device 10,110, 210 may extend into the defect opening or neck 190 or into branchvessels.

For some embodiments, as discussed above, the device 10, 110, 210 may bemanipulated by the user to position the device 10, 110, 210 within thevascular site or defect 160 during or after deployment but prior todetachment. For some embodiments, the device 10, 110, 210 may be rotatedin order to achieve a desired position of the device 10 and, morespecifically, a desired position of the permeable shell 40, 140, 240,340, 440, prior to or during deployment of the device 10, 110, 210. Forsome embodiments, the device 10, 110, 210 may be rotated about alongitudinal axis of the delivery system 112 with or without thetransmission or manifestation of torque being exhibited along a middleportion of a delivery catheter being used for the delivery. It may bedesirable in some circumstances to determine whether acute occlusion ofthe vascular defect 160 has occurred prior to detachment of the device10, 110, 210 from the delivery apparatus 111 of the delivery system 112.These delivery and deployment methods may be used for deployment withinberry aneurysms, terminal aneurysms, or any other suitable vasculardefect embodiments 160. Some method embodiments include deploying thedevice 10, 110, 210 at a confluence of three vessels of the patient'svasculature that form a bifurcation such that the permeable shell 40 ofthe device 10, 110, 210 substantially covers the neck of a terminalaneurysm. Once the physician is satisfied with the deployment, size andposition of the device 10, 110, 210, the device 10, 110, 210 may then bedetached by actuation of the control switch 188 by the methods describedabove and shown in FIG. 26. Thereafter, the device 10, 110, 210 is in animplanted state within the vascular defect 160 to effect treatmentthereof.

FIG. 27 illustrates another configuration of a deployed and implanteddevice in a patient's vascular defect 160. While the implantationconfiguration shown in FIG. 26 indicates a configuration whereby thelongitudinal axis 46 of the device 10, 110, 210 is substantially alignedwith a longitudinal axis of the defect 160, other suitable andclinically effective implantation embodiments may be used. For example,FIG. 27 shows an implantation embodiment whereby the longitudinal axis46 of the implanted device 10, 110, 210 is canted at an angle of about10 degrees to about 90 degrees relative to a longitudinal axis of thetarget vascular defect 160. Such an alternative implantationconfiguration may also be useful in achieving a desired clinical outcomewith acute occlusion of the vascular defect 160 in some cases andrestoration of normal blood flow adjacent the treated vascular defect.FIG. 28 illustrates a device 10, 110, 210 implanted in an irregularlyshaped vascular defect 160. The aneurysm 160 shown has at least twodistinct lobes 192 extending from the main aneurysm cavity. The twolobes 192 shown are unfilled by the deployed vascular device 10, 110,210, yet the lobes 192 are still isolated from the parent vessel of thepatient's body due to the occlusion of the aneurysm neck portion 190.

Markers, such as radiopaque markers, on the device 10, 110, 210 ordelivery system 112 may be used in conjunction with external imagingequipment (e.g. x-ray) to facilitate positioning of the device ordelivery system during deployment. Once the device is properlypositioned, the device 10 may be detached by the user. For someembodiments, the detachment of the device 10, 110, 210 from the deliveryapparatus 111 of the delivery system 112 may be affected by the deliveryof energy (e.g. heat, radiofrequency, ultrasound, vibrational, or laser)to a junction or release mechanism between the device 10 and thedelivery apparatus 111. Once the device 10, 110, 210 has been detached,the delivery system 112 may be withdrawn from the patient's vasculatureor patient's body 158. For some embodiments, a stent 173 may be placewithin the parent vessel substantially crossing the aneurysm neck 190after delivery of the device 10 as shown in FIG. 19 for illustration.

For some embodiments, a biologically active agent or a passivetherapeutic agent may be released from a responsive material componentof the device 10, 110, 210. The agent release may be affected by one ormore of the body's environmental parameters or energy may be delivered(from an internal or external source) to the device 10, 110, 210.Hemostasis may occur within the vascular defect 160 as a result of theisolation of the vascular defect 160, ultimately leading to clotting andsubstantial occlusion of the vascular defect 160 by a combination ofthrombotic material and the device 10, 110, 210. For some embodiments,thrombosis within the vascular defect 160 may be facilitated by agentsreleased from the device 10 and/or drugs or other therapeutic agentsdelivered to the patient.

For some embodiments, once the device 10, 110, 210 has been deployed,the attachment of platelets to the permeable shell 40 may be inhibitedand the formation of clot within an interior space of the vasculardefect 160, device, or both promoted or otherwise facilitated with asuitable choice of thrombogenic coatings, anti-thrombogenic coatings orany other suitable coatings (not shown) which may be disposed on anyportion of the device 10, 110, 210 for some embodiments, including anouter surface of the filaments 14 or the hubs 66 and 68. Such a coatingor coatings may be applied to any suitable portion of the permeableshell 40. Energy forms may also be applied through the deliveryapparatus 111 and/or a separate catheter to facilitate fixation and/orhealing of the device 10, 110, 210 adjacent the vascular defect 160 forsome embodiments. One or more embolic devices or embolic material 176may also optionally be delivered into the vascular defect 160 adjacentpermeable shell portion that spans the neck or opening 190 of thevascular defect 160 after the device 10 has been deployed. For someembodiments, a stent or stent-like support device 173 may be implantedor deployed in a parent vessel adjacent the defect 160 such that itspans across the vascular defect 160 prior to or after deployment of thevascular defect treatment device 10, 110, 210.

In any of the above embodiments, the device 10, 110, 210 may havesufficient radial compliance so as to be readily retrievable orretractable into a typical microcatheter 61. The proximal portion of thedevice 10, 110, 210, or the device as a whole for some embodiments, maybe engineered or modified by the use of reduced diameter filaments,tapered filaments, or filaments oriented for radial flexure so that thedevice 10, 110, 210 is retractable into a tube that has an internaldiameter that is less than about 0.7 mm, using a retraction force lessthan about 2.7 Newtons (0.6 lbf) force. The force for retrieving thedevice 10, 110, 210 into a microcatheter 61 may be between about 0.8Newtons (0.18 lbf) and about 2.25 Newtons (0.5 lbf).

Engagement of the permeable shell 40, 140, 240 with tissue of an innersurface of a vascular defect 160, when in an expanded relaxed state, maybe achieved by the exertion of an outward radial force against tissue ofthe inside surface of the cavity of the patient's vascular defect 160,as shown for example in FIG. 29. A similar outward radial force may alsobe applied by a proximal end portion and permeable shell 40, 140, 240 ofthe device 10, 110, 210 so as to engage the permeable shell 40 with aninside surface or adjacent tissue of the vascular defect 160. Suchforces may be exerted in some embodiments wherein the nominal outertransverse dimension or diameter of the permeable shell 40 in therelaxed unconstrained state is larger than the nominal inner transversedimension of the vascular defect 160 within which the device 10, 110,210 is being deployed, i.e., oversizing as discussed above. The elasticresiliency of the permeable shell 40 and filaments 14 thereof may beachieved by an appropriate selection of materials, such as superelasticalloys, including nickel titanium alloys, or any other suitable materialfor some embodiments. The conformability of a proximal portion of thepermeable shell 40, 140, 240 of the device 10, 110, 210 may be such thatit will readily ovalize to adapt to the shape and size of an aneurysmneck 190, as shown in FIGS. 20-22, thus providing a good seal andbarrier to flow around the device. Thus, the device 10 may achieve agood seal, substantially preventing flow around the device without theneed for fixation members that protrude into the parent vessel.

Although the foregoing invention has, for the purposes of clarity andunderstanding, been described in some detail by way of illustration andexample, it will be obvious that certain changes and modifications maybe practiced which will still fall within the scope of the appendedclaims.

What is claimed is:
 1. A device for treatment of a patient's cerebralaneurysm, comprising: a first permeable shell having a proximal end, anelongate proximal extension, a distal end, a radially constrainedelongated state configured for delivery within a catheter lumen, anexpanded state with a longitudinally shortened configuration relative tothe radially constrained state, and a plurality of elongate filamentsthat are woven together to form a mesh, the expanded state having aproximal end with a recessed section; and a second permeable shellhaving a proximal end, a distal end, a radially constrained elongatedstate configured for delivery within the catheter lumen, an expandedstate with a longitudinally shortened configuration relative to theradially constrained state, and a plurality of elongate filaments thatare woven together to form a mesh, wherein the expanded state of thesecond permeable shell is configured to sit within the recessed sectionof the first permeable shell, wherein the proximal end of the firstpermeable shell is coupled with the distal end of the second permeableshell through the elongate proximal extension of the first permeableshell, and wherein the elongate proximal extension allows for the firstpermeable shell to deflect at an angle relative to a longitudinal axisof the second permeable shell.
 2. The device of claim 1, wherein therecessed section is concave in shape.
 3. The device of claim 2, whereinthe expanded state of the second permeable shell further contains adistal convex section at the distal end of the second permeable shell,wherein the distal convex section is configured to receive the elongateproximal extension of the first permeable shell.
 4. The device of claim1, wherein the first and second permeable shells are formed from thesame plurality of filaments.
 5. The device of claim 1, wherein theplurality of filaments forming the first permeable shell is differentfrom the plurality of filaments forming the second permeable shell. 6.The device of claim 1, further comprising a proximal hub attached to theproximal end of the second permeable shell.
 7. The device of claim 1,further comprising a distal hub attached to a distal end of the firstpermeable shell.
 8. The device of claim 1, wherein the proximal end ofthe second permeable shell is coupled to a pusher.
 9. A cerebralsidewall aneurysm treatment device, comprising: a first permeable shellhaving a proximal end, an elongate proximal extension, a distal end, aradially constrained elongated state configured for delivery within acatheter lumen, an expanded state with a longitudinally shortenedconfiguration relative to the radially constrained state, and aplurality of elongate filaments that are woven together to form a mesh,the expanded state having a proximal end with a recessed section; and asecond permeable shell having a proximal end, a distal end, a radiallyconstrained elongated state configured for delivery within the catheterlumen, an expanded state with a longitudinally shortened configurationrelative to the radially constrained state, and a plurality of elongatefilaments that are woven together to form a mesh, wherein the distal endof the second permeable shell is coupled to the proximal end of thefirst permeable shell, and wherein the proximal end of the secondpermeable shell is coupled with a delivery pusher, wherein the secondpermeable shell is configured to exert force against the recessedsection of the first permeable shell in order to position the firstpermeable shell over a neck region of the cerebral sidewall aneurysm,and wherein the elongate proximal extension allows for the firstpermeable shell to deflect at an angle relative to a longitudinal axisof the second permeable shell.
 10. The device of claim 9, wherein theelongate proximal extension of the first permeable shell comprises aproximal end, and wherein the proximal end of the elongate proximalextension sits within the recessed section.
 11. The device of claim 10,wherein the first permeable shell further comprises an elongate distalextension and a distal concave section, wherein at least a portion ofthe elongate distal extension sits within the distal concave section ofthe first permeable shell.
 12. The device of claim 11, wherein theelongate distal extension is longer than the elongate proximal extensionof the first permeable shell.
 13. The device of claim 10, wherein thefirst permeable shell and second permeable shell are coupled through theelongate proximal extension.
 14. The device of claim 10, wherein theelongate proximal extension is a wire braid.
 15. The device of claim 10,wherein a length of the elongate proximal extension is smaller than aheight of the recessed section.
 16. The device of claim 9, wherein thefirst permeable shell is capable of deflecting relative to alongitudinal axis formed by the pusher and the second permeable shell.17. The device of claim 9, wherein the first permeable shell is capableof deflecting at an angle up to about 1800 relative to a longitudinalaxis formed by the pusher and the second permeable shell.
 18. A devicefor treatment of a patient's cerebral aneurysm, comprising: a firstpermeable shell having a proximal end, an elongate proximal extension, adistal end, a radially constrained elongated state configured fordelivery within a catheter lumen, an expanded state with alongitudinally shortened configuration relative to the radiallyconstrained state, and a plurality of elongate filaments that are woventogether to form a mesh, the expanded state having a proximal end with arecessed section adapted to sit over a neck of an aneurysm; and a secondpermeable shell having a proximal end, a distal end, a radiallyconstrained elongated state configured for delivery within the catheterlumen, an expanded state with a longitudinally shortened configurationrelative to the radially constrained state, and a plurality of elongatefilaments that are woven together to form a mesh, wherein the distal endof the second permeable shell is coupled with the proximal end of thefirst permeable shell, wherein the second permeable shell is configuredto occupy the recessed section of the first permeable shell to augmentsurface coverage over the neck of the aneurysm, and wherein the elongateproximal extension allows for the first permeable shell to deflect at anangle relative to a longitudinal axis of the second permeable shell. 19.The device of claim 18, wherein the second permeable shell does notextend proximally past a plane defined by the proximal most edge of thefirst permeable shell when the first permeable shell is in the expandedstate and the second permeable shell is in its expanded state whereby itis configured to occupy the recessed section of the first permeableshell.
 20. The device of claim 18, wherein the distal end of the secondpermeable shell is coupled with the proximal end of the first permeableshell through the elongate proximal extension.